Genetic variants of immunoglobulin (Ig) kappa chains in laboratory rats (determined by the RI-1 locus) have been shown to differ by 15% of their constant region sequence, raising many questions regarding Ig evolution. Recent studies have shown the RI-1b (LEWIS) serotype to be antigenically complex, and that these antigenic speificities are widely distributed, in different combinations, among rats of other species and genera. The objectives of this proposal are to examine the serological structure of kappa chains from a variety of rats native to Asia and Australia in relation to that of laboratory rats, using alloantisera made monospecific by absorption as well as heteroantisera made between rat species. Australian Rattus species are a uniquely valuable system for such studies, as a result of their well-established evolutionary and toxomic status, their availability as laboratory stocks, and their demonstrated heterogeneity of RI-1 phenotype. Light chains from selected species will be subjected to trypsin digestion, peptide fingerprinting and amino acid sequence determination, to correlate defined antigenic specificities with known sequence differences. Studies will be carried out on the possible production by inbred rats of kappa chain allotypes supposedly absent from their genotype, testing the idea that these kappa chain variants may be the products not of allelic genes, but of tandemly duplicated genes with an allelic control mechanism. An attempt will also be made, using RI-1 congenic rat strains, to test for homology between the chromosomal region coding for kappa chains in mice and rats. The results of these studies will have a direct bearing on the mechanisms involved in the evolution and inheritance of immunoglobulins, the structural basis for Ig antigenicity and immunogenicity, and the possible phylogenetic significance of kappa chain allotypes.